Fesoterodine, an advanced antimuscarinic for the treatment of overactive bladder: A safety update

The pillars of pharmacotherapy for overactive bladder (OAB) are antimuscarinic agents which inhibit bladder seoth muscle contractions through interference with acetylcholine action on muscarinic receptors of the detrusor smooth muscle. Despite the availability of different antimuscarinic compounds, physicians and patients remain dissatisfied with current treatments due to adverse events and/or insufficient efficacy. Therefore, new agents with improved safety and efficacy profiles are needed for a more effective treatment of overactive bladder. Fesoterodine is a novel bladder-selective muscarinic antagonist that has shown potent antimuscarinic activity in vitro and in vivo. In multiple investigations, the agent has been shown to be safe and well tolerated in subjects of different ethnic origin, age and gender; in poor and extensive CYP206 metabolizers; in subjects taking concomitant medication inhibiting CYP3A4; in fed or fasted states; and in those suffering from hepatic impairment. No clinically relevant changes in heart rate, blood pressure, ECG parameters or laboratory analyses have been seen with therapeutic doses of fesoterodine in these studies. Furthermore, in a phase II clinical trial in patients with OAB, fesoterodine demonstrated rapid and significant efficacy on a variety of endpoints. The results of this trial encouraged the manufacturer (SCHWARZ PHARMA) to initiate a phase iii clinical trrial program for fesoterodine.